Cholbam (cholic acid)

The recommended dosage of cholic acid for the management of adult and pediatric patients with bile acid synthesis disorders due to single enzyme defects or the adjunctive management of adult and pediatric patients with bile acid synthesis disorders due to peroxisomal disorders is 10-15 mg/kg daily given in 1 or 2 divided doses.

The recommended dosage of cholic acid for the management of bile acid synthesis disorders due to single enzyme defects or the adjunctive management of bile acid synthesis disorders due to peroxisomal disorders and concomitant familial hypertriglyceridemia is 11-17 mg/kg daily given in 1 or 2 divided doses. Patients with newly diagnosed familial hypertriglyceridemia or a family history of the condition may have poor absorption of cholic acid from the intestine and require a 10% increase in the usual recommended dosage to account for losses due to malabsorption. To assess whether the dosage is sufficient in such patients, the clinical response (e.g., presence of steatorrhea) and laboratory values (e.g., AST, ALT, and bilirubin concentrations; prothrombin time (PT)/INR) should be monitored.

The calculated dosage should be rounded to the nearest whole capsule strength available using the 50- or 250-mg capsules either alone or in combination. For more detailed information on selection of capsule strengths to provide a specific dosage of this drug, the dosage tables in the manufacturer's labeling should be consulted.

The lowest dosage required to effectively maintain liver function should be administered. Treatment with cholic acid should be discontinued if liver function does not improve within 3 months of initiation of therapy.

Cholic acid is administered orally with food. Capsules should be swallowed whole and should not be chewed or crushed. Doses should be taken at least 1 hour before or 4-6 hours (or as long an interval as possible) after administration of an aluminum-containing antacid or bile acid sequestrant. (See Drug Interactions: Aluminum-containing Antacids and Drug Interactions: Bile Acid Sequestrants.)

For patients unable to swallow the capsules whole, the capsules may be twisted open gently and the entire contents mixed with 15-30 mL of either infant formula or breast milk for younger children or soft foods (e.g., mashed potatoes, applesauce) for older children to mask any unpleasant taste. The mixture should be stirred for 30 seconds and administered immediately thereafter. The capsule contents will remain as fine granules in the mixture and will not dissolve.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Cholic Acid/Bile Salt Efflux Pump (Bsep) Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: BSEP inhibitors, such as cyclosporine, decrease the amount of conjugated cholic acid secreted into the bile.(1)

CLINICAL EFFECTS: Concurrent use of a BSEP inhibitor may increase the accumulation of conjugated bile salts in the liver, resulting in exacerbation of liver impairment.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid the concurrent use of cholic acid with BSEP inhibitors such as cyclosporine. If concurrent use is warranted, monitor serum transaminases and bilirubin. Instruct patients to report any signs of worsening liver impairment, such as yellowing of the whites of the eyes or skin, dark or brown (tea-colored) urine, pain on the right side of the stomach, bleeding or bruising that occurs more easily than normal, or increased lethargy.(1)

DISCUSSION: BSEP inhibitors, such as cyclosporine, decrease the amount of conjugated cholic acid secreted into the bile. Concurrent use of these agents with cholic acid may increase the accumulation of conjugated bile salts in the liver, resulting in exacerbation of liver impairment.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Cholic Acid/Aluminum-Based Antacids; Bile Acid Sequestrants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum-based antacids and bile acid sequestrants may decrease the gastrointestinal absorption of cholic acid.(1)

CLINICAL EFFECTS: Simultaneous administration of an aluminum-based antacid or a bile acid sequestrant may result in decreased absorption and effectiveness of cholic acid.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: For maximal bioavailability in patients receiving both medications, administer cholic acid at least 1 hour before or 4-6 hours after (or as great an interval as possible) a bile acid sequestrant or aluminum-based antacid.(1)

DISCUSSION: Aluminum-based antacids have been shown to adsorb cholic acid in vitro. Bile acid sequestrants reduce bile acid absorption.(1)

The manufacturer states there are no known contraindications to the use of cholic acid.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Disease of liver

Adverse effects reported in clinical studies in 1% or more of patients receiving cholic acid include diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.

More Frequent

• Jaundice
• Skin rash

Less Frequent

• Polyp of intestine

Rare or Very Rare

• Abnormal hepatic function tests
• Cholestasis

More Frequent

• Abdominal pain with cramps
• Diarrhea
• Malaise
• Nausea
• Peripheral neuropathy
• Reflux esophagitis
• Urinary tract infection

No enhanced messaging available.

Safety and efficacy of cholic acid have not been established in infants younger than 3 weeks of age.

There are no studies assessing associated risk of cholic acid therapy in pregnant women or animals. In a study of 15 patients with bile acid synthesis disorders due to single enzyme defects treated with cholic acid for a median of 12 years, 4 normal pregnancies in 2 patients resulted in the birth of 4 healthy infants; however, these limited data may not adequately predict the presence or absence of risk during pregnancy.

A pregnancy surveillance program (COCOA Registry (Cholbam(R): Child and Mother's Health)) that monitors pregnancy outcomes in women exposed to cholic acid during pregnancy has been established. Women who become pregnant while exposed to cholic acid during pregnancy are encouraged to enroll themselves in the pregnancy registry, or their clinicians may enroll them in the registry by calling 844-202-6262.

Endogenous cholic acid is distributed into human milk; there are no data in nursing women or lactating animals to determine whether exogenously administered cholic acid is distributed into milk. The effects of cholic acid on nursing infants or on milk production are unknown. The benefits of breast-feeding and the importance of cholic acid to the woman should be considered along with the potential adverse effects on the breast-fed child from the drug or the underlying maternal condition.

Clinical trials of cholic acid did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults.